Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001721138 | SCV000235149 | likely benign | not provided | 2020-12-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002517796 | SCV000285748 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000617307 | SCV000736705 | likely benign | Cardiovascular phenotype | 2021-06-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000182764 | SCV001338641 | likely benign | not specified | 2020-04-13 | criteria provided, single submitter | clinical testing | Variant summary: RYR2 c.7925G>A (p.Arg2642Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 249184 control chromosomes, predominantly at a frequency of 0.0011 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 44- fold the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.7925G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. They have cited the variant as likely benign (n=2) and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
Color Diagnostics, |
RCV001188652 | SCV001355743 | likely benign | Cardiomyopathy | 2019-01-27 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003917692 | SCV004742619 | likely benign | RYR2-related condition | 2022-11-10 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |